In human, antibody medicines targeting immune checkpoint molecules, which are immunosuppressive molecules has lately drawn attention and many clinical trials thereof have been conducted. In particular, clinical trials for human cancer that target PD-1 (Programmed cell death 1) and PD-L1 (programmed cell death 1 ligand-1) have achieved excellent results and drawn attention as a next-generation cancer therapy (see non-Patent Documents 1 and 2).
PD-1 is a receptor on the surface of T cells. It has the function of suppressing activation of T cells and shown to have the function of suppressing the immune response against the self, etc. Such suppression of the immune response is achieved by binding of PD-L1, a ligand of PD-1, to PD-1. Cancer cells express PD-L1 and gain the ability to suppress the activation of T cells and evade immune response by binding of expressed PD-L1 to PD-1. Therefore, inhibiting binding between PD-1 and PD-L1 is considered to be effective in treating cancer.
So far, a cancer therapeutic agent comprising an anti-PD-L1 antibody as an active ingredient and having the effect of suppressing the proliferation of cancer cells in vivo (see Patent Document 1) and an anticancer agent comprising an anti-PD-1 antibody or an anti-PD-L1 antibody, functioning to restore the responsiveness of iNKT cells in which allergy has been induced by administration with an iNKT cell ligand (see Patent Document 2) have been proposed. Moreover, the development of anti-PD-1 antibodies as therapeutic agents for melanoma, non-small cell lung cancer, and renal cell cancer is in progress (see Non Patent Document 3).
The number of cancer cases of pets has been rapidly increased in these days due to the longevity of pets. Cancer therapies for pets, as well as those for humans, have progressed and the three major therapies of surgical, radiation, and chemical (anticancer agent) therapies have been performed positively.
In Japan, dogs are the most common household pets and approximately 13 million dogs are kept. Therefore, the number of cancer cases in dogs is increasing. For treating cancer of dogs, the aforementioned three major therapies employed conventionally have a limit and therapies targeting an immune checkpoint molecule such as PD-1 or PD-L1 are expected to be a new therapy that can be used instead of or along with the three major therapies. However, there has been a problem that antibody medicines for human PD-1 and PD-L1 are not effective in dogs. The development of antibodies against canine PD-1 and canine PD-L1 has been therefore demanded. However, studies on PD-1 and PD-L1 in dogs had not progressed: the expression of PD-1 and PD-L1 cDNAs in dogs was not confirmed and the production of antibodies recognizing canine PD-1 and PD-L1 was difficult.